Deficiency of the Complement Component 3 but Not Factor B Aggravates Staphylococcus aureus Septic Arthritis in Mice.

Abstract

The complement system plays an essential role in the innate immune response and protection against bacterial infections. However, detailed knowledge regarding the role of complement in Staphylococcus aureus septic arthritis is still largely missing. In this study, we elucidated the roles of selected complement proteins in S. aureus septic arthritis. Mice lacking the complement component 3 (C3(-/-)), complement factor B (fB(-/-)), and receptor for C3-derived anaphylatoxin C3a (C3aR(-/-)) and wild-type (WT) control mice were intravenously or intra-articularly inoculated with S. aureus strain Newman. The clinical course of septic arthritis, as well as histopathological and radiological changes in joints, was assessed. After intravenous inoculation, arthritis severity and frequency were significantly higher in C3(-/-)mice than in WT controls, whereas fB(-/-)mice displayed intermediate arthritis severity and frequency. This was in accordance with both histopathological and radiological findings. C3, but not fB, deficiency was associated with greater weight loss, more frequent kidney abscesses, and higher bacterial burden in kidneys. S. aureus opsonized with C3(-/-)sera displayed decreased uptake by mouse peritoneal macrophages compared with bacteria opsonized with WT or fB(-/-)sera. C3aR deficiency had no effect on the course of hematogenous S. aureus septic arthritis. We conclude that C3 deficiency increases susceptibility to hematogenous S. aureus septic arthritis and impairs host bacterial clearance, conceivably due to diminished opsonization and phagocytosis of S. aureus.

• Authors: Manli Na, Anders Jarneborn, Abukar Ali, Amanda Welin, Malin Magnusson, Anna Stokowska, Marcela Pekna, Tao Jin
• Journal: Infection and immunity (Infect Immun) Vol. 84 Issue 4 Pg. 930-939 (Apr 2016) ISSN: 1098-5522 [Electronic] United States
• PMID: 26787717 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Na et al.

Chemical References

• C3a-derived anaphylatoxin receptor, mouse
• Complement C3
• Receptors, G-Protein-Coupled
• Complement Factor B

Topics

• Animals
• Arthritis, Infectious (genetics, immunology)
• Complement C3 (genetics, metabolism)
• Complement Factor B (genetics, metabolism)
• Gene Expression Regulation (physiology)
• Macrophages, Peritoneal (physiology)
• Mice
• Mice, Knockout
• Phagocytosis (physiology)
• Receptors, G-Protein-Coupled (genetics, metabolism)
• Staphylococcal Infections (immunology, pathology)
• Staphylococcus aureus